Factores predictivos de displasia en adenomas de colon / Predictive factors of dysplasia in colon adenomas / Fatores de displasia preditiva em adenomas de cólon

RESUMEN Introducción: los pólipos colorrectales son elevaciones circunscritas de la mucosa, la mayoría son asintomáticos, que constituyen un factor de riesgo del cáncer colorrectal. Objetivo: identificar la relación existente entre variables como la edad, sexo, índice de masa corporal, endoscópicas e histológicas y el riesgo de presentar displasia en la lesión resecada. Métodos: se realizó un estudio de cohorte en pacientes que se les practicó colonoscopia y tuvieron diagnóstico histológico de adenoma de colon, atendidos en el servicio de gastroenterología del hospital Provincial Universitario Carlos Manuel de Céspedes, desde el 1ro de septiembre de 2016 hasta el 31 de agosto de 2019. Resultados: se estudiaron 83 pacientes, la edad media fue de 60.9 años, el sexo masculino aportó el 61.4% de los casos, como promedio el índice de masa corporal fue de 25 Kg/m2, el tamaño promedio de las lesiones fue de 11.2mm, el adenoma tubular fue el más frecuente (88/119), las lesiones se localizaron con mayor frecuencia en el sigmoides (34/119) y la morfología polipoidea sésil aportó el 52.9%. En el análisis multivariado el tamaño mayor de 8mm, la localización distal, la morfología plana y el componente velloso incrementaron la probabilidad de displasia. Conclusiones: la aparición de displasia fue más frecuente entre la quinta y sexta décadas de la vida, así como en las lesiones mayores de ocho milímetros. Se comprueba el valor cimero del componente velloso del adenoma, el tamaño mayor de ocho milímetros, la localización distal y la morfología plana como los factores de mayor asociación con el riesgo de desarrollar la displasia en los adenomas colónicos.

ABSTRACT Introduction: colorectal polyps are circumscribed elevations of the mucosa, most of which are asymptomatic, which constitute a risk factor for colorectal cancer. Objective: to identify the relationship between variables such as age, sex, body mass index, endoscopic and histological and the risk of presenting dysplasia in the resected lesion. Methods: a cohort study was carried out in patients who underwent colonoscopy and had a histological diagnosis of colon adenoma, treated at the gastroenterology service of the Carlos Manuel de Céspedes Provincial Universitario Hospital, from September 1, 2016 to December 31, August 2019. Results: 83 patients were studied, the average age was 60.9 years, the male sex contributed 61.4% of the cases, on average the body mass index was 25 Kg/m2, the average size of the lesions It was 11.2mm, the tubular adenoma was the most frequent (88/119), the lesions were located more frequently in the sigmoid (34/119) and the sessile polypoid morphology contributed 52.9%. In the multivariate analysis, the size greater than 8mm, the distal location, the flat morphology and the hairy component increased the probability of dysplasia. Conclusions: the appearance of dysplasia was more frequent between the fifth and sixth decades of life, as well as in lesions larger than eight millimeters. The top value of the hairy component of the adenoma, the size greater than eight millimeters, the distal location and the flat morphology are verified as the factors of greatest association with the risk of developing dysplasia in colonic adenomas.

RESUMO Introdução: pólipos colorretais são elevações circunscritas da mucosa, a maioria é assintomática, que são um fator de risco para o câncer colorretal. Objetivo: identificar a relação entre variáveis como idade, sexo, índice de massa corporal, endoscópico e histológico e o risco de displasia na lesão seca. Métodos: foi realizado estudo de coorte em pacientes que fizeram colonoscopia e tiveram diagnóstico histológico de adenoma de cólon, atendido no serviço de gastroenterologia do Hospital Universitário Provincial Carlos Manuel de Céspedes, de 1º de setembro de 2016 a 31 de agosto de 2019. Resultados: foram estudados 83 pacientes, a idade média foi de 60,9 anos, o sexo masculino contribuiu com 61,4% dos casos, em média, o índice de massa corporal foi de 25 Kg/m2, o tamanho médio das lesões foi de 11,2mm, o adenoma tubular foi o mais comum (88/119), as lesões foram mais frequentemente localizadas no sigmoide (34/119) e a morfologia polipóíide sessile contribuiu com 52,9%. Na análise multivariada, o tamanho maior de 8mm, localização distal, morfologia plana e componente peludo aumentou a probabilidade de displasia. Conclusões: o início da displasia foi mais comum entre a quinta e a sexta décadas de vida, bem como em lesões superiores a oito milímetros. O valor cimero do componente peludo do adenoma, o tamanho maior de oito milímetros, a localização distal e a morfologia plana são verificados como os fatores mais associados ao risco de desenvolver displasia em adenomas colonicos.

Expression and Clinical Significance of TKTL1 in Colon Adenoma and Colon Cancer / 胃肠病学

Background: TKTL1 is expressed in various tumor tissues, and its expression level is closely related to tumor invasion, metastasis and prognosis. Aims: To investigate the expression and clinical significance of TKTL1 in colon adenoma and colon cancer. Methods: Thirty normal colon mucosa, 84 colon adenoma confirmed by colonoscopy, and 84 colon cancer tissues diagnosed by surgery from March 2015 to May 2018 at the First Hospital of Zibo were enrolled. Protein expression of TKTL1 was detected by immunohistochemistry, and its relationship with clinicopathological parameters in patients with colon adenoma, colon cancer were analyzed. Results: Rate of TKTL1 expression was significantly increased in colon adenoma and colon cancer than in normal colon mucosa (57.1%, 85.7% vs. 13.3%, P0.05). The expression of TKTL1 was not related to gender, age, differentiation in patients with colon cancer (P>0.05), while was related to TNM staging, distant metastasis, lymph node metastasis and depth of infiltration (P<0.05). Conclusions: The expression of TKTL1 in colon adenoma and colon cancer is significantly higher than that in normal colon tissues, and is related to the staging and metastasis of colon cancer. The expression of TKTL1 is closely related to the occurrence and development of colon cancer.

Study on the Absorption of Silymarin Enteric Coated-PLGA Nanoparticles in Rat in situ Intestine Perfu-sion Model and Caco-2 Cell Model / 中国药房

OBJECTIVE:To study the absorption features of Silymarin enteric coated-polyllactic-co-glycolic acid (PLGA) nanoparticles in rat in situ intestine perfusion model and colonic adenoma Caco-2 cell model. METHODS:HPLC method was used to determine the content of silymarin. The absorption rate constant(Ka)and apparent absorption coefficient(Kapp)of Silymarin sus-pension,Silymarin PLGA nanoparticles and Silymarin enteric coated-PLGA nanoparticles were investigated in duodenum,jejunum, ileum and colon of rat in situ intestine perfusion model;the apparent permeability coefficient (Papp) of those drugs containing low-concentration,medium-concentration and high-concentration(20,40,60 μg/mL)of silymarin in Caco-2 cell model were also investigated. RESULTS:Compared with Silymarin suspension,Ka and Kapp of Silymarin PLGA nanoparticles and Silymarin enteric coated-PLGA nanoparticles were all increased in duodenum,jejunum,ileum and colon(P0.05). CONCLUSIONS:Silymarin enteric coated-PLGA nanoparticles can effectively increase the intestinal ab-sorption,cellular uptake and transmembrane transport rate of silymarin.

Abdominal Obesity, Insulin Resistance, and the Risk of Colonic Adenoma / 대한소화기학회지

BACKGROUND/AIMS: Abdominal obesity and hyperinsulinemia or insulin resistance are of interest in connection with colon carcinogenesis. We conducted a prospective case controlled study for the evaluation of relationship between abdominal obesity, insulin resistance, and colorectal adenoma. METHODS: Fifty patients with colorectal adenoma and fifty healthy subjects were included in this study. Total colonoscopic examinations were performed in all the subjects. Fasting blood sugar (FBS), insulin, homeostasis model assessment (HOMA-IR), triglyceride (TG), cholesterol (CROL), BMI (body mass index), WHR (waist hip ratio), percent body fat (PBF) and obesity degree (OD) were measured. HOMA-IR was considered to represent insulin resistance. Diabetic patients were excluded from this study. RESULTS: There were no differences in sex, serum insulin, FBS, HOMA-IR, TG, CROL between adenoma and control group. Subjects with high BMI, WHR, percent body fat, and obesity were more likely to have colonic adenoma. Multiple logistic regression analysis after adjusting confounding factors, had revealed that WHR was the most important independent risk factor for colon adenoma. CONCLUSIONS: Abdominal obesity was most closely related to colonic adenoma. However, insulin resistance was not related to colonic adenoma. A larger case controlled study is needed.

The Characteristics of Colonic Adenoma Detected by 18F-FDG-PET / 대한소화기내시경학회지

BACKGROUND/AIMS: FDG-PET is widely used for the evaluation of cancer patients. FDG-PET is usually employed for a staging of colorectal cancer and for the early detection of postoperative recurrence of cancer. Areas of focal uptake that suggest colonic lesions, including benign adenoma, may be seen on an FDG-PET image. This study evaluated the characteristics of colonic adenoma as detected by FDG-PET. METHODS: 60 subjects (M/F: 30:30, mean age: 55+/-11) who underwent both PET study and colonoscopy were enrolled and their data were retrospectively analyzed. RESULTS: A total of 50 lesions of colonic adenoma (3~35 mm) were found in 17 subjects by colonoscopy. Compared with the colonoscopic findings, FDG- PET had a positive predictive value of 52.9% and a negative predictable value of 81.4%. The positive rate increased with the size of the colonic adenoma (15 mm, 100.0%; > or =10 mm, 82.4%; <5 mm, 0.0%) and with the protruded type of polyp (sessile, 25.0%; subpedunculated, 47.7%; pedunculated, 90.9%). CONCLUSIONS: FDG-PET positive colonic lesions should raise a concern for not only possible malignancy, but also for the large sized or malignant transforming colonic adenoma.

Expression of Cyclooxygenase-2 and p53 Protein in Colonic Adenoma with Malignant Change / 대한소화기내시경학회지

BACKGROUND/AIMS: The aim of this study was to investigate the value of expression of COX-2 and p53 protein in colonic adenoma with or without malignant change. METHODS: We studied twenty-five cases of colonic adenoma with malignant change and twenty-five cases of colonic adenoma without malignant change treated by colonoscopic polypectomy in Chungnam National University Hospital from January, 1999 to July, 2002. We compared the expression of COX-2 and p53 protein by immunohistochemical stain in both group. RESULTS: In immunohistochemical staining, the expression of COX-2 was demonstrated 68.0% (17 of 25) of colonic adenoma with malignant change and not different with that of colonic adenoma without malignant change. The overexpression of p53 protein was detected immunohistochemically in 88.0% (22 of 25) of colonic adenoma with malignant change and 32% (8 of 25) of colonic adenoma only (p <0.05). CONCLUSIONS: The degree of COX-2 expression was similar in colonic adenoma and colonic adenoma with malignant change, but the expression of p53 in colonic adenoma with malignant change was significantly higher (p <0.05). These results suggest COX-2 might operate on early step of adenoma-carcinoma sequence. Also these results remind us that mutation of p53 gene operates on the late step of adenoma-carcinoma sequence.

Colonic Uptake Patterns of F-18-FDG PET in Asymptomatic Adults: Comparison with Colonoscopic Findings / 대한핵의학회잡지

PURPOSE: Physiologic intestinal FDG uptake is frequently observed in asymptomatic individuals for cancer screening FDG PET. Colonic FDG accumulation is a well-known confusing findings that interfere true cancer detection or cause false positive. The aim of this study was to evaluate the pattern and intensity of colonic uptake in whole body FDG PET in asymptomatic healthy adults and to correlate them with colonoscopic findings. MATERIALS AND METHODS: We reviewed retrospectively 64 subjects (age: 27-87, M: F = 31: 33 ) who underwent both FDG PET and colonoscopy for cancer screening. FDG uptake patterns were classified as focal, segmental and diffuse. Maximum SUV were measured. The PET results were compared with colonoscopic and histologic findings. RESULTS: In 13 patients FDG bowel uptake was interpreted as focal, in 17 patients as segmental and in 34 patients as diffuse uptake. Six adenomas (17.6%, average diameter =5.0 mm) were found in diffuse pattern, 7 adenomas (41.1%, 5.6 mm) in segmental and 4 adenomas and 1 adenocarcinoma (38.5%, 16.4 mm) in focal uptake pattern. In patients with focal uptake, four were non-adenomatous pathologic lesions (30.8%, 2 intestinal tuberculosis, 2 mucosal ulcer). There is no difference of mean SUV between patients with adenoma and with negative colonoscopic results in each group of intestinal FDG pattern (Diffuse: 1.7 +/- 0.1 vs. 1.9 +/- 0.5, Segmental: 4.8 +/- 3.6 vs. 4.2 +/- 1.2, Focal: 6.5 +/- 4.7 vs. 3.5 +/- 1.3). Large adenomas (> 1 cm) can be detected more in the focal uptake pattern (4 out of 5) rather than in segmental (1 out of 7) or diffuse uptake (none) and had higher SUV (6.3 +/- 4.8) than small adenomas (3.5 +/- 3.0) (statistically insignificant). CONCLUSION: Focal FDG uptake is associated more often with large adenoma and other pathologic findings in colonoscopy. Segmental uptake cannot discriminate presence of adenoma from negative results, while diffuse pattern may have more chance to be normal.

Using MCM2 as A Novel Cell Replication Marker in Diagnosing Colorectal Carcinoma / 中国普外基础与临床杂志

Objective To study the current research status of minichromosome maintenance protein 2 (MCM2), the cell cycle proliferation marker, in the diagnosis of colorectal carcinoma. Methods Literatures about the application of MCM2 in the study of colorectal carcinoma were collected and reviewed.Results MCM2, as a marker of cell dysplasia and malignancy, was usually used in the study of carcinoma. The study on expression of MCM2 in the cell of colorectum in different proliferational stage might help to screen colorectal carcinoma as early as possible. Conclusion As a relatively specific and sensitive marker of cell proliferation, MCM2 might become a promising mark for diagnosing colorectal carcinoma in the early stage.

A case of multiple colonic adenomas which were found incidentally in FDG-PET / 대한내과학회지

Positron emission tomography (PET), performed after administration of F-18-fluoro-2-deoxy-D-glucose (FDG), has been shown to be useful in detection of a wide variety of tumors. It is now well established that many malignancies show increased FDG uptake due to enhanced glycolytic rate compared with surrounding benign tissues. Colorectal cancer is avid for FDG, and preliminary studies suggest a strong potential role of FDG-PET scanning in imaging studies of patients with colorectal cancer. On the FDG-PET image, areas of focal FDG accumulations suggesting colonic lesions may be seen, in asymptomatic patients. Colonoscopy, regarded as the gold standard for the detection of both polyp and cancer, should be performed in such cases. We experienced a case of multiple colonic adenomas, which were incidentally found as two masses of intensely increased FDG uptake in proximal transverse colon and splenic flexure. We confirmed the adenomas by colonoscopy and herein report this case with a review of literature.

Two Cases of Colon Adenocarcinoma Transformed from Colonic Adenoma / 대한소화기내시경학회지

The prevalence of colorectal cancer is increasing now in Korea and the principal strategy of its management is early detection and surgical resection. Current discussion of the topic of colorectal polyps and cancer is largely based on the concept of the adenoma-carcinoma sequence, which is thought to be the most probable pathogenesis for colorectal cancer. But the case reports about colonic adenocarcinoma arising from adenoma in clinical practice between short interval are rare in Korea. We experienced two cases of colon cancer, which were transformed from small adenoma can not be removed because of patients' refusal, 3 years ago. So we present these cases with a review of relevant literatures.

An Association between Apolipoprotein E Genotype and Colonic Adenomas in Korean / 대한소화기내시경학회지

BACKGROUND/AIMS: Apolipoprotein E polymorphism plays an important role in the metabolism of cholesterol and bile acids, which may be related to the development of colorectal adenomas. An association between apolipoprotein E genotype and colonic adenomas has been reported in a western country. This study was designed to determine whether the apolipoprotein E was genotype would be associated with proximal or distal colonic adenomas in Koreans. METHODS: On the colonoscopy, colonic adenomas were found in 132 patients. Proximal colonic adenoma was found in 35 patients and distal colonic adenoma was found in 97 patients. Serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride were measured. Apolipoprotein E genotype was determined by PCR and allele specific oligonucleotide hybridization. 279 control subjects without an adenoma on the screening sigmoidoscopy were selected randomly. RESULTS: The serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride did not significantly differ between each adenoma group and control group. The individual frequencies of epsilon2, epsilon3 and epsilon4 alleles in patients with colonic adenomas did not differ from those in control subjects. The frequency of either heterozygote or homozygote for epsilon4 allele in patients with proximal adenoma was lower than that in control subjects (0.029 vs 0.168, p<0.05). CONCLUSIONS: The data suggest that epsilon4 allele may be associated with a lower risk for the development of proximal colonic adenoma in Korean men.

Clinicopathological Analysis of Suspicious Attenuated Adenomatous Polyposis Coli

Familial adenomatous polyposis (FAP) is an inherited autosomal dominant syndrome caused by germ-line mutations of the adenomatous polyposis coli (APC) gene. Clinical diagnosis of familial adenomatous polyposis is usually based on the presence of >100 colonic adenomas, which, if left untreated, progress to colorectal cancer, typically at age under 40 years. Attenuated adenomatous polyposis coli is a variant of familial adenomatous polyposis and also has been described as "hereditary flat adenoma syndrome". Attenuated adenomatous polyposis coli is recognized by the occurrence of or =5 or > or =10) colonic adenomas. It is tend to be located proximal to splenic flexure and a later onset of colorectal carcinoma than familial adenomatous polyposis. PURPOSE: This study was performed to analyze the clinicopathologic features of suspicious attenuated adenomatous polyposis coli, to document the occurrence of colorectal carcinoma, and to assess the definition of attenuated adenomatous polyposis coli. METHODS: From June 1989 to June 1998, we reviewed 773 cases of colonic adenomas and compared with three groups (Group I, II, III) at Asan Medical Center. Median follow-up period was 16.4 months (range, 1 to 102 months). RESULTS: The incidence of suspicious attenuated adenomatous polyposis coli (Group II) was 4.9%. The most common symptom was anal bleeding (36.9%). Median size and number of adenomas were 1.0 cm (0.2 to 7.5 cm), 2 (1 to 43), respectively.Location of adenoma was prevalent at right colon in Group II (P<0.05). In respect to the occurrence of carcinoma in situ (CIS), it was more frequently presented in Group II (13.5%) and Group III (13.6%) whereas 4.1% in Group I (P<0.05). Recurrence rates within 12 months after polypectomy or surgery in Group II was 13.5% whereas 5.6% in Group I (P<0.05). CONCLUSIONS: Histopathology revealed suspicious attenuated adenomatous polyposis coli with villous component to be relatively correlated with occurrence of colorectal carcinoma. In suspicious attenuated adenomatous polyposis coli (Group II), the interval of the recurrence of the polyps was shorter than the control group with right colonic predominancy. These findings might be associated with genetic codominance of APC gene or other mutator genes.

bcl-2 and p53 Gene Expression in Colonic Adenoma and Carcinoma / 대한암학회지

PURPOSE: Recently, it is suggested that the inhibitian of apoptosis is associated with tumorigenesis of colon. Bcl-2 gene is an important inhibitory regulator of apoptosis, and bcl-2 acts antagonistly with the wild type p53 gene, one of the tumor suppressor genes, in apoptosis. To detnmine the role of bcl-2 and p53 gene in colonic tumorigenesis, we performed the study. MATERIALS AND METHODS: We tested the tissue obtained by polypectomy and surgical resection by immunohistochemical staining for Bcl-2 and p53. RESULTS: We found that in normal colonic tissue, the Bcl-2 was sparcely expressed, and the p53 was expressed sporadically. The rate of positivity of staining was below 5%. However, in colonic adenoma and colon cancer tissue, Bcl-2 and p53 were expressed more than in nonnal colonic tissue(p<0.05). (Scoring in Colonic adenoma: Bcl-2 6.2+/-1.1, p53 5.7+/-1.0; Scoring in Colonic carcinoma: Bcl-2 4.7+/-1.0, p53 8.3+/-0.9) CONCLUSION: Our results suggested that the bcl-2 and p53 play an important role in colonic tumorigenesis.

Clinicopathoalogic Features of Colonic Flat Adenoma / 대한내과학회지

OBJECTIVES: To determine accurate diagnosis and proper treatment, we reviewed colonoscopic and histologic findings of flat adenoma of colon, METHODS: We studied retrospectively 2148 cases of colonoscopic findings performed in our hospital from March of 1993 to September of 1995. RESULTS: 1) The incidence of adenoma is 9.5%(203 cases), and that of flat adenoma is 1.6%(34 cases). 2) The location of flat adenoma is 3 cases in rectum(8.8%), 15 cases in sigmoid colon(44.1%), 9 cases in descending colon(26.5%), 3 cases in transverse colon(8.8%) and 4 cases in ascending colon and cecum(11.8%). 3) The diameter of flat adenoma was smaller than 5mm in 17 cases(50.0%), between 5-10mm in 8 cases(23.5%) and larger than 10mm in 9 cases (26.5%). Mean size was 9.2mm. 4) In colonoscopic features, type IIa was 25 cases (73.5%), type IIa + IIc was 5 cases(14.7%) and lateral spreading tumor was 4 cases(11.8%). 5) In histologic findings, tubular adenoma was 26 cases(76.5%), tubulovillous adenoma was 6 cases (17.6%) and serrated adenoma was 2 cases(5.9%). 6) The incidence of severe dysplasia or carcinoma was zero in smaller than 5mm, 25.0%(2 case) in 5-10mm and 55.6%(5 cases) in larger than 10mm. 7) The incidence of severe dysplasia or carcinoma was 11.5%(3 cases) in tubular adenoma and 66.7%(6 cases) in tubulovillous adenoma. 8) It was confirmed by abdominal CT scan or operation that lesions were limited to intraepithelium in 4 cases, mucosa in 2 cases submucosa in 1 case and no lymph node metastasis in any case. CONCLUSION: Even though flat adenoma of colon was smaller than polypoid adenoma, the incidence of malignant change was higher. When it was smaller than 10mm, the incidence of submucosal invasion or lymph node invasion was rare. Therefore endoscopic mucosal resection(EMR) can be the treatment of choice in flat adenoma smaller than 10mm, and after EMR, it is desirable to decide the treatment modality depending on the histologic findings.